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Healthcare Headlines
Genome Biology - Latest Articles
  • Sequencing three crocodilian genomes to illuminate the evolution of archosaurs and amniotes
    The International Crocodilian Genomes Working Group (ICGWG) will sequence and assemble the American alligator (Alligator mississippiensis), saltwater crocodile (Crocodylus porosus) and Indian gharial (Gavialis gangeticus) genomes. The status of these projects and our planned analyses are described.

  • Dissecting the regulatory architecture of gene expression QTLs
    Background: Expression quantitative trait loci (eQTLs) are likely to play an important role in the genetics of complex traits; however their functional basis remains poorly understood. Using the HapMap lymphoblastoid cell lines, we combine 1000 Genomes genotypes and an extensive catalogue of human functional elements to investigate the biological mechanisms that eQTLs perturb. Results: We use a Bayesian hierarchical model to estimate the enrichment of eQTLs in a wide variety of regulatory annotations. We find that ~40% of eQTLs occur in open chromatin, and that they are particularly enriched in transcription factor binding sites, suggesting that many directly impact protein-DNA interactions. Analysis of core promoter regions shows that eQTLs also frequently disrupt some known core promoter motifs but, surprisingly, are not enriched in other well-known motifs such as the TATA box. We also show that information from regulatory annotations alone, when weighted by the hierarchical model, can provide a meaningful ranking of the SNPs that are most likely to drive gene expression variation. Conclusions: Our study demonstrates how regulatory annotation and the association signal derived from eQTL-mapping can be combined into a single framework. We used this approach to further our understanding of the biology that drives human gene expression variation, and of the putatively causal SNPs that underlie it.

  • MetaMerge: scaling up genome-scale metabolic reconstructions, with application to Mycobacterium tuberculosis
    Reconstructed models of metabolic networks are widely used for studying metabolism in various organisms. Many different reconstructions of the same organism often exist concurrently, forcing researchers to choose one of them at the exclusion of the others. We describe MetaMerge, an algorithm for semi-automatically reconciling a pair of existing metabolic network reconstructions into a single metabolic network model. We use MetaMerge to combine two published metabolic networks for Mycobacterium tuberculosis into a single network which allows many reactions that could not be active in the individual models to become active, and predicts essential genes with a higher positive predictive value.

  • Uberon, an integrative multi-species anatomy ontology
    We present Uberon, an integrated cross-species ontology consisting of over 6500 classes representing a variety of anatomical entities, organized according to traditional anatomical classification criteria. The ontology represents structures in a species-neutral way and includes extensive associations to existing species-centric anatomical ontologies, allowing integration of model organism and human data. Uberon provides a necessary bridge between anatomical structures in different taxa for cross-species inference. It uses novel methods for representing taxonomic variation, and has proved to be essential for translational phenotype analyses. Uberon is available at http://obo.svn.sourceforge.net/viewvc/obo/uberon/releases/2011-09-25/

  • SpliceGrapher: Detecting patterns of alternative splicing from RNA-seq data in the context of gene models and EST data
    We propose a method for predicting splice graphs that enhances curated gene models using evidence from RNA-Seq and EST alignments. Results obtained using RNA-Seq experiments in Arabidopsis thaliana show that predictions made by our SpliceGrapher method are more consistent with current gene models than predictions made by TAU and Cufflinks. Furthermore, analysis of plant and human data indicates that the machine learning approach used by SpliceGrapher is useful for discriminating between real and spurious splice sites, and can improve the reliability of detection of alternative splicing. SpliceGrapher is available for download at http://SpliceGrapher.sf.net.

  • The dog particle
    {no abstract}

  • Co-survival of the fittest few: mosaic amplification of receptor tyrosine kinases in glioblastoma
    Mosaic amplification of receptor tyrosine kinases in glioblastoma suggests that tumor cells with different progression driver mutations may coevolve rather than compete during clonal evolution.

  • Dynamic systems
    A report of the Wellcome Trust Functional Genomics and Systems Biology Conference, Hinxton, UK, 29 November to 1 December 2011.

  • Low-cost sequencing opens new insights into diverse plant genomes
    A report on the Plant Genomes and Biotechnology: From Genes to Networks meeting, held at Cold Spring Harbor Laboratory, 30 November to 3 December 2011.

  • DNA-protein interactions in high definition
    An elegant, genome-wide approach to define the precise DNA sequences bound by transcription factors has been developed by Rhee and Pugh.


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